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Transcranial Focal Electric Stimulation Avoids P-Glycoprotein Over-Expression during Electrical Amygdala Kindling and
Daniel Fonseca-Barriendos1, José Luis Castañeda-Cabral2, Frida Martínez-Cuevas1
1Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, Ciudad de México C.P. 14330, Mexico.
Life (Basel, Switzerland)
|June 28, 2023
Summary
P-glycoprotein (P-gp) overexpression increases during epileptogenesis, contributing to hyperexcitability. Transcranial focal electrical stimulation (TFS) effectively inhibits this P-gp increase, suggesting a novel therapeutic strategy for preventing epilepsy.
Area of Science:
- Neuroscience
- Epileptology
- Pharmacology
Background:
- P-glycoprotein (P-gp) overexpression is implicated in neuronal hyperexcitability and epileptogenesis.
- Transcranial focal electrical stimulation (TFS) has shown potential in delaying epileptogenesis and reducing P-gp overexpression post-seizure.
Purpose of the Study:
- To measure P-gp expression levels during the progression of epileptogenesis.
- To determine if the antiepileptogenic effects of TFS are linked to the inhibition of P-gp overexpression.
Main Methods:
- Electrical amygdala kindling (EAK) was induced in male Wistar rats.
- P-gp expression was quantified in relevant brain areas at different stages of epileptogenesis.
- TFS was applied daily after EAK stimulation to assess its impact on P-gp levels.
Main Results:
- P-gp expression significantly increased in the hippocampus and neocortex with the progression of EAK, correlating with seizure severity.
- TFS administration effectively prevented the EAK-induced overexpression of P-gp in the hippocampus and neocortex.
- The study observed structure-specific and seizure-dependent changes in P-gp expression.
Conclusions:
- EAK-induced P-gp overexpression is associated with neuronal hyperexcitability and epileptogenesis.
- TFS demonstrates efficacy in inhibiting P-gp overexpression, suggesting a potential therapeutic strategy for preventing epilepsy.
- Targeting P-gp could offer a novel approach for managing epileptogenesis in high-risk individuals.

